Estrogen enhances retrograde transport of brain-derived neurotrophic factor in the rodent forebrain

The neurotrophins and their receptors activate signaling molecules to regulate neural function in development and adulthood. Neurons in the septum-diagonal band complex (or basal forebrain) derive neurotrophins through retrograde transport of these peptides from their forebrain targets. The present study tests the hypothesis that the gonadal hormone estrogen enhances retrograde transport of the neurotrophin brain-derived neurotrophic factor (BDNF). Estrogen increases BDNF expression in the horizontal limb of the diagonal band of Broca (hlDBB) and its forebrain target the olfactory bulb. In the present study, rhodamine-labeled (Rho-) BDNF injected into the olfactory bulb was rapidly transferred to neurons in the hlDBB. Significantly greater numbers of hlDBB neurons were retrogradely labeled with Rho-BDNF in animals pretreated with estrogen, compared with placebo-replaced controls. Anti-tyrosine kinase (trk) B antibodies injected into the olfactory bulb attenuated retrograde transport of Rho-BDNF in a dose-dependent manner, suggesting that estrogen may enhance BDNF transport in this circuit through regulation of its trk receptor. Anti-trkB antibodies also reduced cAMP response element binding protein phosphorylation in the hlDBB and combined injections of anti-trkA and trkB in the olfactory bulb reduced estrogen-induced increases in basal forebrain choline acetyltransferase. These studies support the hypothesis that estrogen facilitates neurotrophin transport in forebrain circuits.